non-active liver metastases (NLM) in a Phase 1 trial (n~150) and randomized Phase 2 trial (n~230) in October 2023. We are pursuing a global regulatory strategy and aim to
initiate submission of a biologics license application (BLA) to the FDA for a potential accelerated approval by the end of 2024, followed by a planned submission to the European Medicines Agency in the first half of 2025.
We have established collaborations with several companies, including Bristol-Myers Squibb Company (BMS), Betta Pharmaceuticals
Co., Ltd. (Betta), UroGen Pharma Ltd. (UroGen), Gilead Sciences, Inc. (Gilead), and Incyte Corporation (Incyte). These collaborations, along with our internal programs, have resulted in over a dozen
antibody programs progressing to pre-clinical or clinical development.
Our collaboration
agreement with Incyte grants Incyte exclusive licenses for monospecific antibodies targeting GITR, OX40, TIM-3, LAG-3, and an undisclosed target. Incyte has been
advancing these antibodies in clinical trials. Incyte has terminated the OX40 program, effective October 2023, and has notified us of their intent to terminate both the GITR program and undisclosed program, effective May 2024. Upon termination, the
rights to the OX40, GITR, and undisclosed programs revert back to us. Incyte is responsible for all future development expenses for the remaining programs, and we are eligible to receive up to an additional $315.0 million in potential milestone
payments, along with royalties on future sales.
In September 2018, through our subsidiary Agenus Royalty Fund, LLC, we entered into a
royalty purchase agreement with XOMA (US) LLC. Pursuant to the agreement, XOMA purchased 33% of all future royalties and 10% of all future milestone payments that we are entitled to receive from Incyte and Merck, after considering our obligations to
a third party. As of December 31, 2023, we remain eligible to receive up to $283.5 million and $76.5 million in potential development, regulatory, and commercial milestones from Incyte, after accounting for our obligations under the
XOMA Royalty Purchase Agreement.
In December 2018, we entered into collaboration agreements with Gilead for the development and
commercialization of up to five novel I-O therapies. Gilead received worldwide exclusive rights to our bispecific antibody, AGEN1423, and the exclusive option to license AGEN1223, a bispecific antibody, and
AGEN2373, a monospecific antibody. All three assets are currently in clinical development. Gilead elected to return AGEN1423 to us in November 2020 and terminated the license agreement. We ceased development of AGEN1223 in the third quarter of 2021,
and the option and license agreement for AGEN1223 were formally terminated in October 2021. The AGEN2373 option agreement remains in place, and we are responsible for developing the program until the option decision point. If Gilead exercises the
option, we may opt-in to share development and commercialization costs in the United States in exchange for a 50:50 profit (loss) share and revised milestone payments. In March 2022, we received a
$5.0 million clinical milestone under the AGEN2373 option agreement. Pursuant to the terms of the AGEN2373 option agreement, we remain eligible to receive a $50.0 million option exercise fee and up to an additional $520.0 million in
aggregate milestone payments, as well as royalties on future sales. In November 2019, we entered into a license agreement with UroGen, granting them an exclusive, worldwide license (not including Argentina, Brazil, Chile, Colombia, Peru, Venezuela
and their respective territories and possessions) to develop, manufacture, and commercialize zalifrelimab for the treatment of cancers of the urinary tract via intravesical delivery. We received an upfront payment of $10.0 million and are
eligible to receive up to $200.0 million in milestone payments, as well as royalties on future sales.
In June 2020, we entered into
a license and collaboration agreement with Betta, granting them an exclusive license to develop, manufacture, and commercialize balstilimab and zalifrelimab in Greater China. We received an upfront payment of $15.0 million and are eligible to
receive up to $100.0 million in milestone payments, as well as royalties on future sales in Greater China.
In May 2021, we entered
into a License, Development, and Commercialization Agreement with BMS for our pre-clinical anti-TIGIT bispecific antibody program, AGEN1777. BMS received an exclusive worldwide